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A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113)
  1. Isabelle Ray-Coquard1,2,
  2. Helen Hatcher3,
  3. Emmanuelle Bompas4,
  4. Antonio Casado5,
  5. Annekke Westermann6,
  6. Nicolas Isambert7,
  7. Paolo Giovanni Casali8,
  8. Sarah Pratap9,
  9. Daniel Stark10,
  10. Claudia Valverde11,
  11. Anjana Anand12,
  12. Manon Huizing13,
  13. Anne Floquet14,
  14. Lars Lindner15,
  15. Barbara Hermes16,
  16. Beatrice Seddon17,
  17. Corneel Coens18,
  18. Robin Jones19 and
  19. Nick Reed20
  1. 1 Centre Leon Berard, Lyon, Rhône-Alpes, France
  2. 2 Oncology, Université Claude Bernard Lyon 1, Villeurbanne, Auvergne-Rhône-Alpes, France
  3. 3 medical oncology, Cambridge University, Cambridge, Cambridgeshire, UK
  4. 4 Medical Oncology Department, ICO, Saint Herblain, Pays de la Loire, France
  5. 5 Medical Oncology Department, Complutense University of Madrid, Madrid, Comunidad de Madrid, Spain
  6. 6 Medical Oncology Department, Academisch Medisch Centrum, Amsterdam, North Holland, The Netherlands
  7. 7 Medical Oncology Department, Centre Georges-François Leclerc, Dijon, Bourgogne-Franche-Comté, France
  8. 8 Medical Oncology Department, IRCCS, Milano, Lombardia, Italy
  9. 9 Medical Oncology Department, Oxford University, Oxford, Oxfordshire, UK
  10. 10 Medical Oncology Department, Leeds Teaching Hospitals NHS Trust, Leeds, Leeds, UK
  11. 11 Medical Oncology Department, Vall d'Hebron Hospital, Barcelona, Catalunya, Spain
  12. 12 Medical Oncology Department, Nottingham Trent University, Nottingham, Nottinghamshire, UK
  13. 13 Medical Oncology Department, Universitair Ziekenhuis Antwerpen, Edegem, Antwerp, Belgium
  14. 14 Medical Oncology Department, Institut Bergonié, Bordeaux, Aquitaine, France
  15. 15 Medical Oncology Department, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
  16. 16 Medical Oncology Department, Eberhard Karls Universitat Tubingen, Tubingen, Baden-Württemberg, Germany
  17. 17 Medical Oncology Department, University College London, London, London, UK
  18. 18 Statistics and Quality of Life, EORTC, Brussels, Belgium
  19. 19 Medical Oncology, Royal Marsden Hospital NHS Trust, London, London, UK
  20. 20 Medical Oncology, NHS Greater Glasgow and Clyde, Glasgow, Glasgow, UK
  1. Correspondence to Professor Isabelle Ray-Coquard, Centre Leon Berard, Lyon, Rhône-Alpes, France; isabelle.ray-coquard{at}lyon.unicancer.fr

Abstract

Background Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas.

Primary objective To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy.

Study hypothesis Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo

Trial design This is a randomized double blinded phase II trial.

Major inclusion/exclusion criteria The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma.

Primary endpoint Progression-free survival at 4 months.

Sample size The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020.

Trial registration number ClinicalTrials.gov, number NCT01979393.

  • uterine cancer
  • sarcoma
  • adenosarcoma
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Footnotes

  • Contributors All authors included patients. IR-C, NR and CC designed the trial.

  • Funding This study was funded by European Organisation for Research and Treatment of Cancer and Ligue Nationale de Lutte contre le Cancer (France).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Data availability statement There are no data in this work

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